Abstract

Aberrant activation of Anaplastic Lymphoma Kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor.

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Author details

  1. Jikui Guan

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  2. Ganesh Umapathy

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Yasuo Yamazaki

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  4. Georg Wolfstetter

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  5. Patricia Mendoza

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  6. Kathrin Pfeifer

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  7. Ateequrrahman Mohammed

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  8. Fredrik Hugosson

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  9. Hongbing Zhang

    Five Prime Therapeutics Inc., South San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Amy W Hsu

    Five Prime Therapeutics Inc., South San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Robert Halenbeck

    Five Prime Therapeutics Inc., South San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Bengt Hallberg

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  13. Ruth H Palmer

    Department of Medical Biochemistry and Cell Biology, Instititute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    For correspondence
    ruth.palmer@gu.se
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Roger Davis, Howard Hughes Medical Institute & University of Massachusetts Medical School, United States

Version history

  1. Received: July 1, 2015
  2. Accepted: September 28, 2015
  3. Accepted Manuscript published: September 29, 2015 (version 1)
  4. Version of Record published: November 24, 2015 (version 2)

Copyright

© 2015, Guan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jikui Guan
  2. Ganesh Umapathy
  3. Yasuo Yamazaki
  4. Georg Wolfstetter
  5. Patricia Mendoza
  6. Kathrin Pfeifer
  7. Ateequrrahman Mohammed
  8. Fredrik Hugosson
  9. Hongbing Zhang
  10. Amy W Hsu
  11. Robert Halenbeck
  12. Bengt Hallberg
  13. Ruth H Palmer
(2015)
FAM150A and FAM150B are activating ligands for Anaplastic Lymphoma Kinase
eLife 4:e09811.
https://doi.org/10.7554/eLife.09811

Share this article

https://doi.org/10.7554/eLife.09811

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